中文摘要：

目的应用聚肌胞苷酸（polyinosinic polycytidylic acid，poly I：C）建立原发性胆汁性肝硬化（PBC）动物模型。方法80只C57BL／6雌性小鼠，分为空白对照组（5只）、poly I：C5mg／kg组（25只）和10mg／kg组（25只）、阴性对照组（25只）。poly I：C5和10mg／kg组小鼠腹腔分别注射poly I：C5和10mg／kg，每3天1次，阴性对照组用等体积无菌PBS液注射。每4周处死一批小鼠，同时检测血清丙氨酸转氨酶（ALT）、碱性磷酸酶（ALP）、抗核抗体（ANA）、抗线粒体抗体（AMA）水平，肝组织行H-E染色后镜下观察胆管组织学变化；Annexin V检测脾细胞凋亡。结果5mg／kg组第4周小叶间胆管开始出现炎性细胞浸润，浸润的胆管数量随注射时间延长而增加，第20周达51％；血清AMA阳性率逐渐增高，16周达4只（共5只），最高滴度达1：10000。10mg／kg组ANA、AMA均在第8周时明显升高，但随后呈下降趋势，其他指标与5mg／kg组差异无统计学意义（P〉0．05）。5mg／kg组血清ALP显著高于阴性对照组（P〈0．05）。poly I：C两组脾细胞早期凋亡率均明显高于阴性对照组（P〈0．05），但两组间差异无统计学意义（P〉0．05）。阴性对照组仅出现ANA阳性，其他指标均无明显变化。结论poly I：C（5mg／kg）注射16周后可初步建立PBC动物模型。细胞凋亡后释放的自身抗原活化自身反应性淋巴细胞在PBC的发病中可能起重要作用。该模型的建立为今后PBC发病机制和治疗的研究奠定了基础。

英文摘要：

Objective To establish an animal model of primary biliary cirrhosis induced by polyinosinic polycytidylic acid（poly I： C）. Methods Eighty C57BL/6 female mice were divided into blank group （n = 5）, poly I：C 5 mg/kg group （n = 25）, 10 mg/kg group （n = 25） and negative control group （n = 25）. The mice in poly I：C groups were injected with either 5 or 10 mg/kg poly I：C every 3 days. The mice were sacrificed at an interval of 4 weeks to test serum levels of antinuclear antibodies （ANA） and antimitochondrial antibodies（AMA） by immunofluorescence. Liver histological changes were observed by immunochemistry staning with hematoxylin and eosin. Apoptotic cells were detected by Annexin V kit. Results In 5 mg/kg group, infiltration of mononuclear cell was detected in portal areas at 4th week and the number of infiltrated bile ducts increased with injections which reached 51% at 20th week. Meanwhile the positive rate of AMA was increased gradually and reached 80% after 16 weeks with the titer of 1 ： 10 000. The positive rates of AMA and ANA in 10 mg/kg group were first increased at 8th week, then decreased gradually. Compared with control group, alkaline phosphatase （ALP） was also increase significantly in 5 mg/kg group. The number of apoptotic cells in poly I： C groups were higher than that in control group （P 〈 0. 05）, but there was no significant difference between the two groups. Only ANA detected in the sera of control group. Conclusions Animal model of primary biliary cirrhosis can be established by injection of poly I： C（5 mg/kg） after 16 weeks. Autoantigens released from apoptotic cells might be responsible for activating autoreactive lymphocytes which can induce PBC. The successful establishment of model may play an important role in the study of pathogenesis of PBC.